Neurons in the fusiform gyrus are fewer and smaller in autism

Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.
Brain (Impact Factor: 9.2). 05/2008; 131(Pt 4):987-99. DOI: 10.1093/brain/awn033
Source: PubMed


Abnormalities in face perception are a core feature of social disabilities in autism. Recent functional magnetic resonance imaging studies showed that patients with autism could perform face perception tasks. However, the fusiform gyrus (FG) and other cortical regions supporting face processing in controls are hypoactive in patients with autism. The neurobiological basis of this phenomenon is unknown. Here, we tested the hypothesis that the FG shows neuropathological alterations in autism, namely alterations in neuron density, total neuron number and mean perikaryal volume. We investigated the FG (analysing separately layers II, III, IV, V and VI), in seven post-mortem brains from patients with autism and 10 controls for volume, neuron density, total neuron number and mean perikaryal volume with high-precision design-based stereology. To determine whether these results were specific for the FG, the same analyses were also performed in the primary visual cortex and in the cortical grey matter as a whole. Compared to controls, patients with autism showed significant reductions in neuron densities in layer III, total neuron numbers in layers III, V and VI, and mean perikaryal volumes of neurons in layers V and VI in the FG. None of these alterations were found in the primary visual cortex or in the whole cerebral cortex. Although based on a relatively small sample of post-mortem brains from patients with autism and controls, the results of the present study may provide important insight about the cellular basis of abnormalities in face perception in autism.

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    • "This focal disruption of cortical architecture suggests dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. Van Kooten et al. [32] showed significant reductions in neuron densities in layer III, total number of neurons in layers III, V, and VI in the fusiform gyrus, but none of these alterations were found in the primary visual cortex or the whole cerebral cortex. This study provides insight about the cellular basis of abnormalities in face perception in autism. "
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    ABSTRACT: IntroductionA total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.ResultsThe study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.Conclusions The observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism.
    09/2014; 2(1):141. DOI:10.1186/s40478-014-0141-7
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    • "In another neuropsychiatric condition, people with autism have a selective deficit in perceiving facial expressions categorically (Teunisse and de Gelder, 2001) which affects activation of the fusiform gyrus (Pierce et al., 2004). One of the few neuropathological features of the disorder is altered minicolumn organization (Casanova et al., 2006) accompanied by altered neuron density in layer III of the fusiform gyrus (Van Kooten et al., 2008). Although it is not, so far, apparent that the effect in autism is asymmetrical between the hemispheres, it is clear that these alterations present a risk of disruption to the very structures that support lateralized face processing and are consistent with atypical processing in that functional domain. "
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    ABSTRACT: The presence of asymmetry in the human cerebral hemispheres is detectable at both the macroscopic and microscopic scales. The expansion of cortical surface during development and across evolutionary time is largely due to the proliferation and spacing of the microscopic vertical columns of cells that form the cortex. In the asymmetric planum temporale, minicolumn width asymmetry is associated with surface area asymmetry. This asymmetry of minicolumn spacing is absent in the equivalent areas of the brains of other apes.The left hemisphere dominance for speech depends, partly, on a bias for higher resolution processing across widely spaced minicolumns with less overlapping dendritic fields, whereas narrow minicolumn spacing in the right hemisphere is associated with overlapping, low resolution, holistic processing. This concept refines the simple notion that a larger brain area is associated with dominance for a function with a mechanistic explanation associated with ‘processing type’. Face processing provides a test case - it is the opposite of language, being dominant in the right hemisphere. Consistent with the bias for holistic, configural processing of faces, the minicolumns in the right hemisphere fusiform gyrus are narrower than in the left hemisphere, which is associated with featural processing. Again, this asymmetry is not found in chimpanzees.The difference between hemispheres may also be seen in terms of processing speed, facilitated by asymmetric myelination of white matter tracts. By cross-referencing the differences between the active fields of the two hemispheres, via tracts such as the corpus callous, the relationship of local features to global features may be encoded. Altered minicolumn organisation is also observed in neuropsychiatric disorders such as autism and schizophrenia. This may be a consequence of disequilibrium in the processing of local and global features related to disorganisation of asymmetric minicolumnar units o
    Frontiers in Psychology 07/2014; 5:820. DOI:10.3389/fpsyg.2014.00820 · 2.80 Impact Factor
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    • "The majority of the brains of autistic subjects examined in four other morphometric studies [3-5,21] represent a portion of the cohort examined in this study. The reduced volume of neurons detected in 14 of 16 examined subcortical structures, archicortex, and cerebellum, combined with the results of the neocortical and brainstem studies of other investigators, strengthens the hypothesis of the global nature of defective neuronal growth in the brains of autistic subjects. "
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    ABSTRACT: Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon's horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.
    03/2014; 2(1):28. DOI:10.1186/2051-5960-2-28
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